The connective tissues define the form and structure of man and all multicellular animals. The collagen fiber networks within these tissues are the major components, responsible for the stress bearing properties and functional integrity. In different tissues the collagens may differ in peptide sequence and usually appear in tissue specific structures. Several tissues contain mixtures of several collagen types. It has been observed in several pathological situations that the relative contents of collagens of different types may change. Our major objective over the next several years will be to determine how collagen chain type relates to collagen fibril structure. This question cannot be divorced from questions of collagen processing: molecular assembly and selection of chain types; conversion of procollagen to collagen; and, assembly of molecules into microfibrils and higher order fibrils. Questions of molecular assembly and chain selection are to be examined at the protein synthesis level; peptide chain initiation, attachment to the endoplasmic reticulum, chain interaction (selection) and triple-helix formation. Collagen microfibril structure will be examined in vitro by analyses of structure and mechanism, and rates of fibril formation as dependent upon collagen type, state of conversion from procollagen to collagen and the presence of modifying noncollagenous extracellular matrix components. Studies will be extended to the examination of tissues from patients with connective tissue disorders as well as animal models.